Search

Background Peripheral nerve system (PNS) involvement is common in Fabry's disease (FD), predominantly affecting the small nerve fibers that are difficult to investigate with conventional electrophysiological methods. Patients and methods Eighteen patients followed for Fabry's disease underwent a prospective series of electroneurophysiological explorations, including a study of the cardiac parasympathetic autonomic nervous system (ANS) and electrochemical skin conductance (ESC) tests. Data were compared with those obtained in 18 matched healthy controls. Results All patients had at least one clinical sign suggestive of neuropathy: 16 reported an acrosyndrome and 12 had dyshidrosis. Cold hypoesthesia was found in 15 patients and heat hypoesthesia in 13. Electroneurophysiological investigations and study of the cardiac parasympathetic ANS were normal in all patients. The ESC was significantly lower in FD patients compared with controls. Conclusion PNS involvement is common in FD and should be suspected in patients exhibiting an acrosyndrome, dyshidrosis and/or cold hypoesthesia. Conventional electrophysiological investigations are normal. New techniques, such as ESC, provide early diagnosis of small fiber involvement that currently requires more sophisticated tests difficult to apply in routine practice.

Summary The ANAES has defined four stages of chronic renal disease according to the presence of markers of kidney damage and to Cockcroft clearance (an estimate of endogeneous creatinine clearance). Renal insufficiency is defined by a Cockcroft clearance below 60 ml/min per 1.73 m2. Renal insufficiency is moderate if Cockcroft clearance is between 59 and 30 ml/min, severe between 29 and 15 ml/min, and end stage below 15 ml/min. Recommendations for the management of patients are given at each stage. The National Kidney Fundation has defined five stages of chronic kidney disease introducing mild renal insufficiency if estimated glomerular filtration rate is between 89 and 60 ml/min.

Summary Renal function is still evaluated in 2010 by the dosage of serum creatinine. Its main drawback is the lack of sensitivity to detect early renal insufficiency. Formulas allowing to estimate either endogeneous creatinine clearance (Cockcroft formula) or glomerular filtration rate (MDRD and CKD-EPI formulas) give good prediction of renal function. However, they are not accurate in patients with extreme age and body weight, and in patients with a low production of creatine or having normal renal function.

In earlier registry analyses, cyclosporine at doses of3 mg/kg/d at 1 year post-renal transplantation has been associated with significant graft loss or reduction in renal function. Improvements in cyclosporine formulation with increased bioavailability, plus the use of more efficient comedications, may now confer better outcomes. To determine the effect of the 1-year cyclosporine microemulsion (CsA-ME) dose on renal allograft function at 5 years, we analyzed data collected from 2889 patients with documented graft survival to year 5 in a prospective, multinational, observational study-Neoral MOST.Glomerular filtration rate (GFR) at year 1 was 63 +/- 20 mL/min and 59 +/- 22 mL/min at year 5. The multivariate analysis including year 1 CsA-ME dose as factor and GFR at 1 year as covariate revealed the most significant factors affecting GFR at year 5 were 1-year GFR, donor age60 years, and CsA-ME dose at 1 year. Risk factors associated with reduction in 5-year GFR (65 mL/min) included donor or recipient age60 years, delayed graft function, cadaveric donor, previous graft, and acute rejection. CsA-ME dose3 mg/kg/d was found to protect GFR. Analysis of GFR at each year posttransplantation (Wilcoxon model) found 1-year CsA-ME (cutoff 3 mg/kg/d) had a significant effect at each time point.Compared to higher doses, CsA-ME3 mg/kg/d at year 1 posttransplantation is associated with increased preservation of renal allograft function at year 5.

Background Long-term success of renal transplantation depends upon the quality of the donor organ, avoidance of peritransplant and early posttransplant damage (rejection), and optimal maintenance of graft function after the first 6-12 months. Glomerular filtration rate (GFR) at 1 year is a standard way to evaluate short-term success, whereas calculated GFR at 5 years gives a better appreciation of long-term outcomes. The objective of this study was to assess the effect of various demographic and transplant-related parameters on renal function via GFR at 1 year and 5 years post transplantation, using univariate and multivariate data analysis. Methods Data on 1-year GFR were available from 10,397 patients, whereas 2,889 patients provided data on both 1-year and 5-year GFR. All patients were enrolled in the Neoral Multinational Observational Study in Transplantation (Neoral-MOST), an ongoing, prospective, observational study of adult renal transplant recipients. Results One-year GFR was the most relevant predictor for 5-year GFR. In a multifactorial analysis (ANCOVA) using 1-year GFR as a continuous variable, the effects of several highly relevant parameters from univariate analysis (such as acute rejection and delayed graft function) on 5-year GFR appeared to be fully mediated by their influence on 1-year GFR, whereas immunological risk factors like HLA match or previous transplantation had an ongoing effect on graft function beyond year 1. Conclusions The findings of this study corroborate and augment data from previous registry surveys, and confirm the importance of observational studies in investigating the role of peritransplant parameters on long-term graft outcome.

OBJECTIVE—Insulin resistance may be a risk factor for diabetic microangiopathy, which may have a familial component. We carried out a family-based study to determine which components of the insulin resistance syndrome are associated with diabetic retinopathy and nephropathy in type 1 diabetes. RESEARCH DESIGN AND METHODS—The Genesis France-Belgium Study is a multicenter binational study designed to investigate the genetic factors involved in the microvascular complications of type 1 diabetes using a family-based design. Probands were type 1 diabetic patients with diabetic retinopathy (classified as background, preproliferative, or proliferative) and possibly diabetic nephropathy (absent, incipient, established, or advanced). The insulin resistance score of their first-degree relatives was calculated according to their BMI and history of arterial hypertension, lipid disorders, and type 2 diabetes. RESULTS—The insulin resistance score of relatives was positively correlated with the albumin excretion rate (P = 0.0009) and fasting plasma glucose (P = 0.0003) and HbA1c (P < 0.0001) concentrations. This score was higher in the relatives of probands with than in those without diabetic nephropathy (P = 0.0370). Similarly, it was higher in relatives of subjects with proliferative diabetic retinopathy than in those of probands without, even after controlling for subjects with versus without diabetic nephropathy (P = 0.0379). However, the components of the insulin resistance score in relatives differed according to the severity of diabetic retinopathy or nephropathy in the probands. Obesity and history of arterial hypertension were most common in relatives of probands with proliferative diabetic retinopathy, whereas obesity and history of lipid disorders were most common in the relatives of probands with diabetic nephropathy. CONCLUSIONS—Familial insulin resistance segregates with diabetic complications: lipid disorders and obesity segregate with diabetic nephropathy, whereas arterial hypertension and obesity segregate with diabetic retinopathy.

Summary Objective: To determine whether Belzer solution (Viaspan®, Bristol-Myers Squibb, Brussels, Belgium), which is more expensive than Eurocollins solution, was better at preventing delayed graft function (DGF) and whether it was cost-effective as it could potentially reduce post-transplantation complications. Method: The risk of occurrence of complications associated with the use of these two rinsing and preserving solutions was estimated from a survey of 106 patients undergoing renal transplantation between 1 January 1993 and 31 March 1998. Both efficacy and adverse outcomes were recorded along with the costs directly associated with the transplantation procedure in the hospital setting: hospitalization, rinsing and preserving solutions, medical and technical interventions and diagnostic tests. Results: For the 45 kidney grafts rinsed and preserved with Eurocollins (strategy S1: n1 = 45) the cost/graft was estimated at 40 €. With Viaspan® (strategy S2: n2 = 61) the corresponding cost/graft was 424 €. Logistic regression analysis showed that Viaspan® was better than Eurocollins solution (eβ = 0·437; P = 0·05) in preventing DGF. Overall, S2 was less expensive than S1, from the hospital's perspective. The mean difference per patient was 278 €, which amounts to a saving of 2% of the total cost per renal transplantation. For rinsing and preserving kidney grafts Belzer solution is therefore preferable to Eurocollins solution.

Introduction L’etiologie du lichen sclero-atrophique (LSA) n’est pas connue. Plusieurs facteurs seraient en cause, dont des mecanismes auto-immuns. Nous rapportons le cas d’une patiente presentant un lichen sclero-atrophique cutaneo-muqueux associe a des anticorps anti-NuMA. Observation Une patiente de 53 ans etait hospitalisee pour la prise en charge d’un LSA diffus. Ses antecedents etaient une insuffisance renale chronique terminale secondaire a une nephropathie interstitielle sur uropathie malformative et 3 fausses couches spontanees tardives. Elle ne prenait aucun medicament. L’examen clinique notait un LSA cutane diffus (abdomen, quatre membres, seins) ainsi qu’un LSA vulvaire severe avec fusion des petites levres et encapuchonnement du clitoris. Elle ne presentait pas de dysurie ni de dyspareunie. Le reste de l’examen clinique etait normal, il n’y avait notamment pas de photophobie, ni arthralgie ou autre manifestation systemique. Une biopsie cutanee du bras gauche revelait des remaniements histologiques du tissu conjonctif, un derme homogeneise avec un aspect fibreux et un collagene epaissi, l’ensemble confirmant le diagnostic de LSA. Le profil biologique auto-immun etait particulier, montrant des anticorps antinucleaires (AAN) a 1/320 avec des anticorps anti-NuMA de type 1. Les recherches d’anticorps anti-ADN, anti-ECT, anticardiolipine, anti-β2GP1 et d’anticoagulant circulant etaient negatives. Discussion Cette observation nous a semblee interessante en raison de l’association d’un LSA cutaneo-muqueux severe et d’un profil auto-immun atypique. L’etiologie du LSA n’est pas connue ; elle semble etre multifactorielle. Son association avec des pathologies inflammatoires et la presence d’auto-anticorps dans 40 % des cas sont en faveur, d’une part, auto-immune. Les anticorps anti-NUMA sont des auto-anticorps antinucleaires rares ( Conclusion Nous rapportons a notre connaissance la premiere observation de la presence d’anticorps anti-NuMA au cours d’un LSA cutaneo-muqueux. La realite et la signification de cette association ne pourront etre etablies qu’a la lumiere d’observations nouvelles.

Resume Introduction. Les transplantations d'organes sont associees a une nette augmentation du risque neoplasique. Plus que l'effet oncogene propre d'une classe therapeutique, c'est le poids total de l'immunosuppression qui semble etre le facteur favorisant predominant. Un oncogene viral est frequemment associe et profite de cet etat d'immunosuppression. Les neoplasies observees ont donc des caracteristiques histologiques, cliniques, evolutives et therapeutiques particulieres. Actualite et points forts. Les mecanismes de l'oncogenese chez les patients immunodeprimes sont progressivement eclaircis. Une infection virale est associee a chaque type neoplasique. Ainsi, les lymphomes B sont lies quasi systematiquement a une infection a Epstein-Barr virus. Les cancers cutanes et les cancers du col uterin succedent souvent a des dysplasies virales secondaires aux papillomavirus. L'augmentation importante de l'incidence des sarcomes de Kaposi montre le role du systeme immunitaire dans le controle de l'infection par le 8 e herpes virus humain. Les cancers hepatiques se rencontrent lors d'infections chroniques par les virus de l'hepatite B ou C. Perspectives et projets. Les complications neoplasiques vont representer un probleme important dans le suivi des transplantes. En effet, le nombre de patients transplantes augmente regulierement. Ces patients ont une duree de vie de plus en plus longue. En outre, les nouveaux medicaments immunosuppresseurs sont de plus en plus puissants. La connaissance precise des mecanismes de controle des cellules neoplasiques et de l'infection virale par le systeme immunitaire sera une etape importante pour permettre une prevention et un traitement efficace de ces cancers. L'etude des liens entre le systeme immunitaire et l'oncogenese virale doit etre un but important de la recherche en transplantation.

Background Delayed graft function (DGF) is a common complication after renal transplantation, and may affect graft function. The aim of this analysis was to evaluate risk factors for DGF, as well as parameters and events influencing graft function after DGF. We analyzed data collected in an ongoing international, prospective; observational study, the Neoral-MOST (Multinational Observational Study in renal Transplantation), and included in the analysis all patients with cadaveric kidney transplants for whom renal function at 1 year posttransplantation was documented ( N = 8950). Logistic regression was used to evaluate the risk factors for DGF occurrence, and multifactorial analysis of variance (ANCOVA) to assess the relevance of different factors for GFR at 1 year. Results Higher donor age, longer CIT, male recipients, Caucasian recipients, high recipients body mass index, and PRA were all associated with a higher risk for DGF. Renal function of former DGF kidneys at 1 year was lower in kidneys of elder donors, or which had experienced rejection or CMV infection. Variations of the maintenance regimen at 1 year posttransplantation were not associated with better graft function. Multifactorial analysis showed donor age and acute rejection as significant independent factors. Conclusions Most factors increasing the risk for DGF or having a negative impact on renal function at 1 year in grafts with DGF are predetermined. Additional posttransplant damage by acute rejection was associated with further reductions in GFR. Preventing acute rejection is an important step in achieving optimal function of DGF grafts.

Hepatitis B (HBV) and hepatitis C (HCV) virus infections are major risk factors affecting long-term morbidity and mortality after renal transplantation. Hepatitis prevalence is subject to geographical variations.To compare and analyze the geographical prevalence, risk factors and impact of HBV and HCV infection in multinational cohorts of renal transplant recipients.From 1989 - 2002, data on 12,856 kidney transplant recipients in 37 countries were collected within the prospective MOST (Multinational Observational Study in Transplantation). Subgroup analyses of hepatitis-related prevalence, risk factors and impact were conducted on patients whose HBV and HCV status was available at time of transplantation. Countries were substratified according to population prevalence ofor = 5% HBV oror = 10% HCV.The prevalence of HBV was 2.9%, of HCV 8.7% and of HBV together with HCV 0.4%. Risk factors for hepatitis infection in renal transplant recipients were long dialysis time, retransplantation and blood transfusions. At each study endpoint up to 5 years after transplantation, no significant differences in graft function were observed, although the 1-year acute rejection rate tended to be lower in HCV+ patients. At 5 years post-transplant, there were no differences between the subgroups and regions regarding infections, post-transplant diabetes mellitus or malignancies including PTLD.Overall, HCV infections are more prevalent than HBV. Despite large geographical differences in prevalence, HBV and HCV status did not appear to have a significant impact on renal graft function, infections, malignancies and post-transplant diabetes mellitus up to 5 years after renal transplantation throughout the MOST countries.

Resume Le but de cette etude est de comparer la nouvelle trousse de dosage du recepteur soluble a l'interleukine 2 (R IL2-S) des Laboratoires Immunotech a celle deja existant des Laboratoires T Cell Sciences. Nous avons teste ses qualites analytiques (performance, sensibilite, reproductibilite), les resultats que nous obtenons dans differents types de prelevement sont bien correles avec ceux donnes par la trousse de reference.

Summary Kidneys obtained from donors after cardiac death (DCD) are known to have higher rates of primary nonfunction and delayed graft function (DGF) than heart beating cadaveric donor (CAD) kidneys, but little is known about long-term function of DCD grafts that survive to 1 year. To investigate the outcomes of renal transplant recipients whose DCD graft functioned for at least 1 year, this study analyzed data collected from 326 DCD graft recipients and 340 CAD-matched controls enrolled in a prospective, multinational, observational study – Neoral®-MOST (Multinational Observational Study in Transplantation) (Novartis, Basel, Switzerland). No differences were found in the demographics or immunosuppression between the two groups. All patients received a Neoral®-based immunosuppressive regimen. Donors after cardiac death graft recipients had a higher incidence of DGF (40% vs. 27% CAD; P

Introduction. Mycophenolate mofetil (MMF) has greatly reduced the risk of acute rejection episodes (ARE) after renal transplantation, but dose reductions/withdrawals could jeopardize long-term results. Methods. The MOST database of de novo patients treated with MMF at month 1 and functioning grafts at month 12 were divided into 2 groups: groups 1, 2 g MMF at month 1 and month 12; and group 2, 2 g MMF at month 1 but MMF

Background Peritransplant risk factors influence short-term and long-term graft survival, and 1-year serum creatinine is known to predict long-term graft survival. To examine interrelationships between risk factors, renal function at 1 year, and long-term graft function in patients maintained on cyclosporine, we analyzed data collected from 10,692 de novo or maintenance renal transplant recipients in an ongoing international, prospective, observational study—Neoral-MOST (Multinational Observational Study in renal Transplantation). The effect of donor age, delayed graft function, acute rejection, donor type, panel-reactive antibodies, and previous graft on 1- and 5-year renal function and their relationship to 1-year serum creatinine was assessed. Results Donor age, delayed graft function, acute rejection, and donor type significantly increased the risk for serum creatinine > 130 μmol/L at 1 year posttransplant, and 1-year serum creatinine was the strongest predictor of 5-year renal function. After adjustment for 1-year serum creatinine, an ongoing influence was observed for donor age, donor type, and previous graft. Delayed graft function and acute rejection had a significant effect on serum creatinine at year 1 but no additional impact on long-term graft function. Conclusions Serum creatinine at 1 year is influenced by risk factors known to affect overall graft survival and is predictive of 5-year renal graft function. The effects of delayed graft function and acute rejection appear to be limited to their influence on serum creatinine at 1 year, whereas donor type and previous graft predominantly affect later stages of graft life.

Background A pivotal role for Type I interferon (IFN) in SLE is supported by gene expression studies that identified the so-called type I IFN signature (IS). Objectives The aim of this study was to improve characterization of the blood-IFN signature in adult SLE patients. Methods Consecutive SLE patients fulfilling the ACR criteria were enrolled and followed-up prospectively. Microarray data were generated using Illumina beadchips. A modular transcriptional repertoire was employed as a framework for the analysis. Results Our repertoire of 260 modules, which consist of co-clustered gene sets, included 3 IFN-annotated modules (M1.2, M3.4 and M5.12) that were strongly up-regulated in SLE patients. At the individual level, a modular IS (ie, over-expression of at least 1 of the 3 IFN modules) was observed in 54/62 (87%) of patients or 131/157 (83%) of samples. The IFN signature was more complex than expected with each module displaying a distinct activation threshold (M1.2 Conclusions Modular repertoire analysis reveals complex IFN signatures in SLE, not restricted to the previous IFN-a signature, but involving also b and g IFNs. These modular IFN signatures may help in the design of disease activity biomarkers. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2405

The dietary intake and urinary solute excretion were evaluated in 49 idiopathic stone formers (SF) and 210 healthy subjects living in the south of France from June, 1990 to September, 1991. The SF consisted of 35 males and 14 females, age 45.6±14 (±SD) years. The healthy subjects consisted of 96 males and 114 females, age 42.4±10 years. The ratio of male/female was greater in the SF. Nutrients and calories were calculated by means of food-composition tables. Twenty-four h urine samples were collected from all subjects and analyzed for urinary excretion of sodium, calcium, phosphorus, uric acid, citrate, magnesium, and oxalate.

We present 8 cases of membranoproliferative glomerulonephritis (MPGN) associated with cryoglobulinemia and hepatitis C virus infection. We think that HVC infection may be searched during diagnostic of MPGN.